This Program Project has the overall objective of defining for the lung the chemical, cellular and physiological characteristics of tissue structure which predispose the lung to injury in vivo. A major portion of the investigation concerns the definition of the content, composition and in vivo functions of the connective tissue components, elastin, collagen and glycosaminoglycans. Studies of the mechanisms of tissue injury to the lung are focussed on proteolysis, the inhibition of proteolysis, the relationship between connective tissue, degradation and resynthesis. An extension of this objective is to define the spatial interrelationships ultrastructurally in situ of connective tissue components in normal lung structure and after proteolytic injury and repair. A related aspect of the overall investigation involves the identification of the specific cells and of their biochemical functions through cell culture techniques and whole lung support cultures to determine the cellular processes which contribute to connective tissue repair and the pathogenetic mechanisms which lead to irreversible structural aterations in lung architecture. This study also concerns the role of the lung parenchyma in the metabolic fate of vasoactive substances including kinins which are transported through the mixed venous circulation to the lung or elaborated in lung tissue. This aspect of the study forms an important link between the cellular functions of lung parenchyma and the role of the lung in homeostatic and pathogenetic mechanisms involving the lung in relation to vasomotor control in the whole organism.